This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. All living beings express those genes whose products are needed most at the given moment. To save resources and provide high adaptability to environmental conditions, organisms developed different systems to sense various physical and chemical cues and transmit them to the machinery that provides selective expression of genes. Though typically the sensing function is performed by proteins, recently discovered regulatory circuits involve mRNA regions, termed riboswitches, capable of direct and specific binding of cellular metabolites. Riboswitches are present in all kingdoms of life, and highly abundant in bacteria, including pathogenic species, where they direct expression of many vital genes in response to various metabolites, including coenzymes, amino acids, sugars, and nucleobases. Each riboswitch is folded into an evolutionary conserved three-dimensional structure stabilized by the interaction with the cognate metabolite. Since riboswitches modulate gene expression through conformational rearrangements in their structures, we have focused our research on the determination of the three-dimensional structures of the riboswitch-ligand complexes. The structures will uncover the molecular principles of riboswitch-controlled gene expression and may help in the rational design of novel classes of metabolite-like antibiotics.